Metabolic Abnormalities in Hispanic Children With Cystic Fibrosis
Status: | Withdrawn |
---|---|
Conditions: | Pulmonary |
Therapuetic Areas: | Pulmonary / Respiratory Diseases |
Healthy: | No |
Age Range: | 7 - 17 |
Updated: | 12/27/2018 |
Start Date: | February 2, 2006 |
End Date: | February 2, 2006 |
Our specific aims include:
1. AIM 1. Characterization of glucose tolerance, nutritional and clinical status,
socioeconomic status, family history of diabetes and genotype in Hispanic CF children
compared to Caucasian CF children. Each child will undergo a two-hour oral glucose
tolerance test and will be categorized by glucose tolerance according to standards set
forth by the 1998 CF Consensus Conference on Diabetes. Nutritional status will be
determined by three-day food journals and intake will be compared to energy needs
measured by indirect calorimetry. Socio-economic status will be calculated from reported
family income and medical insurance coverage. Genotyping will be done at the laboratory
of Dr. Arthur Beaudet at Baylor College of Medicine. Clinical status will be measured
using modified NIH scores. Family history for both type 1 and type 2 diabetes will be
obtained in Spanish by Dr.Vanderwel. This specific aim tests the hypothesis that glucose
intolerance /frank CF related diabetes occurs at a younger age in Hispanics than in
Caucasians with CF, and is correlated to family history of diabetes and clinical status.
2. AIM 2. Characterization of insulin secretion and insulin sensitivity. Previous studies
in adults have described peripheral insulin resistance as a major cause of CF related
diabetes, yet studies have not been conducted in children. Studies in adults and
children without CF suggest that insulin resistance occurs more frequently in Hispanics.
We will measure insulin secretion and insulin sensitivity using the frequently sampled
intravenous glucose tolerance test (IVGTT) and the minimal model analysis of Bergman, as
modified for children. This specific aim tests the hypothesis that Hispanic children
with CF have worse peripheral insulin resistance, but similar insulin secretion when
compared to Caucasian children with CF.
3. AIM 3. Quantification of post-absorptive gluconeogenesis and whole body protein
turnover. Total hepatic glucose production (HGP) will be measured using
[6,6-2H2]glucose. We will quantify gluconeogenesis by measurement of the incorporation
of 2H into the 2nd, 5th and 6th carbons of glucose following 2H20 administration method
of Landau). We will determine whole body protein turnover using the stable isotopes
[1-13C]leucine and will measure serum amino acid levels. This specific aim tests the
hypothesis that gluconeogenesis and whole body protein turnover are disproportionately
higher in Hispanic children and adolescents with CF than in Caucasian CF children.
1. AIM 1. Characterization of glucose tolerance, nutritional and clinical status,
socioeconomic status, family history of diabetes and genotype in Hispanic CF children
compared to Caucasian CF children. Each child will undergo a two-hour oral glucose
tolerance test and will be categorized by glucose tolerance according to standards set
forth by the 1998 CF Consensus Conference on Diabetes. Nutritional status will be
determined by three-day food journals and intake will be compared to energy needs
measured by indirect calorimetry. Socio-economic status will be calculated from reported
family income and medical insurance coverage. Genotyping will be done at the laboratory
of Dr. Arthur Beaudet at Baylor College of Medicine. Clinical status will be measured
using modified NIH scores. Family history for both type 1 and type 2 diabetes will be
obtained in Spanish by Dr.Vanderwel. This specific aim tests the hypothesis that glucose
intolerance /frank CF related diabetes occurs at a younger age in Hispanics than in
Caucasians with CF, and is correlated to family history of diabetes and clinical status.
2. AIM 2. Characterization of insulin secretion and insulin sensitivity. Previous studies
in adults have described peripheral insulin resistance as a major cause of CF related
diabetes, yet studies have not been conducted in children. Studies in adults and
children without CF suggest that insulin resistance occurs more frequently in Hispanics.
We will measure insulin secretion and insulin sensitivity using the frequently sampled
intravenous glucose tolerance test (IVGTT) and the minimal model analysis of Bergman, as
modified for children. This specific aim tests the hypothesis that Hispanic children
with CF have worse peripheral insulin resistance, but similar insulin secretion when
compared to Caucasian children with CF.
3. AIM 3. Quantification of post-absorptive gluconeogenesis and whole body protein
turnover. Total hepatic glucose production (HGP) will be measured using
[6,6-2H2]glucose. We will quantify gluconeogenesis by measurement of the incorporation
of 2H into the 2nd, 5th and 6th carbons of glucose following 2H20 administration method
of Landau). We will determine whole body protein turnover using the stable isotopes
[1-13C]leucine and will measure serum amino acid levels. This specific aim tests the
hypothesis that gluconeogenesis and whole body protein turnover are disproportionately
higher in Hispanic children and adolescents with CF than in Caucasian CF children.
We will recruit 12 Hispanic prepubertal children with CF (ages 7-12, Tanner I) and 12
Hispanic adolescents (ages 15-17, Tanner 3 or 4) from the CF Centers at University of Texas
Southwestern and Baylor College of Medicine in Houston. Information obtained from these
subjects will be compared to 12 prepubertal and 12 adolescent Caucasian children with CF
recruited from the same CF centers. We will categorize the subjects according to glucose
tolerance (OGTT), as well as insulin secretion and insulin sensitivity using the IVGTT and
the Minimal Model, as modified for children. We will also compare the historical information
of socio-economic status and family history. Clinical status will be characterized by
measuring pulmonary function and modified NIH scores, in addition to measuring levels of
circulating cytokines. Gluconeogenesis (GNG) will be quantified by measuring the
incorporation 2H into the 2nd, 5th and 6th carbons of glucose. Whole body protein turnover
(WBPT) will be measured using [1-13C]leucine. Nutritional status will be determined by
three-day food journals, and intake will be compared to energy needs, utilizing indirect
calorimetry to measure resting energy expenditure. Subjects will be recruited from the CF
centers at the University of Texas- Southwestern and the South Central CF Consortium.
Hispanic adolescents (ages 15-17, Tanner 3 or 4) from the CF Centers at University of Texas
Southwestern and Baylor College of Medicine in Houston. Information obtained from these
subjects will be compared to 12 prepubertal and 12 adolescent Caucasian children with CF
recruited from the same CF centers. We will categorize the subjects according to glucose
tolerance (OGTT), as well as insulin secretion and insulin sensitivity using the IVGTT and
the Minimal Model, as modified for children. We will also compare the historical information
of socio-economic status and family history. Clinical status will be characterized by
measuring pulmonary function and modified NIH scores, in addition to measuring levels of
circulating cytokines. Gluconeogenesis (GNG) will be quantified by measuring the
incorporation 2H into the 2nd, 5th and 6th carbons of glucose. Whole body protein turnover
(WBPT) will be measured using [1-13C]leucine. Nutritional status will be determined by
three-day food journals, and intake will be compared to energy needs, utilizing indirect
calorimetry to measure resting energy expenditure. Subjects will be recruited from the CF
centers at the University of Texas- Southwestern and the South Central CF Consortium.
Inclusion Criteria: Subjects will be required to be medically stable at the time of the
study. Medical stability will be defined as:
1. No hospital admission for six weeks or more before the study
2. No oral or intravenous antibiotics for at least six weeks preceding the study
(subjects will be allowed to use low doses of inhaled corticosteroids)
3. Weight-stable (weight deviation less than 2.5 kilograms) for two months prior to the
study.
Exclusion Criteria:
1. Use of oral or intravenous corticosteroid medications within six weeks of the study
2. Evidence of severe liver disease (hepatomegaly, 30% or greater elevation of liver
transaminases, listed for liver transplant)
3. Colonization with Burkholderia cepacia
4. Pregnancy
5. Patients requiring supplemental oxygen.
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